Nurr1 performs its anti-inflammatory function by regulating RasGRP1 expression in neuro-inflammation.
Animals
Cell Line
Chromatin
/ chemistry
DNA-Binding Proteins
/ metabolism
Dopaminergic Neurons
/ metabolism
Guanine Nucleotide Exchange Factors
/ metabolism
HEK293 Cells
Humans
Inflammation
/ metabolism
Introns
Lipopolysaccharides
/ chemistry
Mice
Microglia
/ metabolism
Nuclear Receptor Subfamily 4, Group A, Member 2
/ metabolism
Parkinson Disease
/ metabolism
Signal Transduction
Transcription Factors
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
received:
04
10
2019
accepted:
10
06
2020
entrez:
3
7
2020
pubmed:
3
7
2020
medline:
6
1
2021
Statut:
epublish
Résumé
Nurr1, a transcription factor belonging to the orphan nuclear receptor, has an essential role in the generation and maintenance of dopaminergic neurons and is important in the pathogenesis of Parkinson' disease (PD). In addition, Nurr1 has a non-neuronal function, and it is especially well known that Nurr1 has an anti-inflammatory function in the Parkinson's disease model. However, the molecular mechanisms of Nurr1 have not been elucidated. In this study, we describe a novel mechanism of Nurr1 function. To provide new insights into the molecular mechanisms of Nurr1 in the inflammatory response, we performed Chromatin immunoprecipitation sequencing (ChIP-Seq) on LPS-induced inflammation in BV2 cells and finally identified the RasGRP1 gene as a novel target of Nurr1. Here, we show that Nurr1 directly binds to the RasGRP1 intron to regulate its expression. Moreover, we also identified that RasGRP1 regulates the Ras-Raf-MEK-ERK signaling cascade in LPS-induced inflammation signaling. Finally, we conclude that RasGRP1 is a novel regulator of Nurr1's mediated inflammation signaling.
Identifiants
pubmed: 32612143
doi: 10.1038/s41598-020-67549-7
pii: 10.1038/s41598-020-67549-7
pmc: PMC7329810
doi:
Substances chimiques
Chromatin
0
DNA-Binding Proteins
0
Guanine Nucleotide Exchange Factors
0
Lipopolysaccharides
0
NR4A2 protein, human
0
Nr4a2 protein, mouse
0
Nuclear Receptor Subfamily 4, Group A, Member 2
0
RASGRP1 protein, human
0
Rasgrp1 protein, mouse
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10755Références
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